We propose to establish a National Research Resource for Imaging Mass Spectrometry at Vanderbilt University School of Medicine, Nashville, TN. The Resource would focus on technology advances and innovation that generally would include next generation hardware, software and methods relevant to direct tissue profiling and imaging using mass spectrometry. At the same time, a number of applications in the biological and medical area that would derive significant benefits from this developing technology will be undertaken. In turn, the technical needs of these biological investigations will feed back and help focus and drive additional technology improvement and innovation. The technology program proposed here would involve significant development of histology directed mass spectrometric profiling and imaging of tissues, a new ion source geometry for transmission geometry laser illumination of tissues for single cell analysis, high spatial resolution imaging down to one micron lateral resolution, high sensitivity profiling and imaging to measure lower abundance species than is now possible, and the development of the relevant bio-computational resources to complement the technological advances and enable it to be routinely used by biologists and medical research investigators who are not experts in the field of the technology. The driving biology would be focused on applications that would require new capabilities, such as high spatial resolution imaging of the serotonin neuron proteome in neuro-developmental disorders, studies of breast and prostate cancer, age related macular degeneration, selected stem cell analyses, studies of the glomerulus in diabetic nephropathy, molecular presentations in malformed heart valve development, and aspects of tumor angiogenesis and growth. Important activities of the Resource would also involve selected collaborations of NIH sponsored research that would significantly benefit from the developing technology of Imaging Mass Spectrometry, to offer core capabilities that include secondary ion mass spectrometry for ultra high resolution imaging of low MW species, and FT ICR instrumentation and expertise for ultra high mass spectrometric resolution Training and dissemination of the technology as well as the expertise present in the Resource would be accomplished through a yearly short course, individual scientific visits by established scientists and trainees, and publication of the outcomes of both the technology and applications programs.